Myocardial Viability Research Articles

Abstract 4137349: Cardiomyocyte resilience to Doxorubicin with NAD + supplementation in cardiotoxicity

Introduction: Doxorubicin (DOX) is a potent chemotherapy drug that carries a significant risk of cardiotoxicity leading tso heart failure by presenting a notable challenge in cancer treatment. Despite being characterized by oxidative stress and inflammation, fully understanding Doxorubicin-induced cardiotoxicity (DIC) mechanisms remains elusive. Ongoing research emphasizes the promising role of nicotinamide adenine dinucleotide (NAD + ) and its precursors in cardiovascular health. Therefore, we sought to evaluate the effectiveness of NAD + in preventing or reducing DIC. Methods: H9c2 rat cardiomyocytes were pre-treated with NAD + 100uM for 48 hours, subsequently exposed to DOX 500nM for 24 hours, and received a follow-up NAD + 100uM treatment for an additional 48 hours. Cell viability was evaluated via the MTT assay. Mitochondrial reactive oxygen species (ROS) production was measured using the MitoSOX assay. The expression of genes crucial for cardiac cell development and function was analyzed through quantitative polymerase chain reaction (qPCR). Furthermore, Western blotting (WB) was conducted to detect changes in the expression of proteins associated with oxidative stress and apoptosis, thus providing an in-depth assessment of NAD + 's potential therapeutic effects against anthracycline-induced cardiac complications. Results: NAD + treatment maintained myocardial cell viability in the presence of DOX and modulated gene expression beneficial for cardiac function, including downregulation of pro-inflammatory cytokines such as IL1b and TNF-a. Furthermore, it reduced oxidative stress markers, decreased levels of pro-apoptotic Caspase 3, and increased levels of the antioxidant SOD2 via Sirt1 pathway regulation. Conclusion: Our findings highlight the critical importance of a multidisciplinary research approach to elucidate the cardioprotective capacity of NAD + against DIC, potentially paving the way for new targeted strategies in oncological therapies.

Abstract 4134729: Quantitative, time-efficient viability cardiac magnetic resonance with delayed-phase dynamic contrast enhancement model: a pilot study in dogs with myocardial infarction

Introduction: Late gadolinium enhancement (LGE) is the gold standard for myocardial viability imaging, recommended by all major cardiology societies. In this study, we aimed to develop a time-efficient viability imaging technique utilizing a dynamic contrast enhancement(dDCE) model to shorten the LGE wait time, provide quantitative measures of the contrast washout procedure, and potentially enable a fast and quantitative mean for scar imaging. Methods: A canine study(n=10) was conducted on reperfused myocardial infarction(MI). A dDCE model using dynamic post-contrast T1 maps was adopted to depict the contrast washout process. dDCE maps were reconstructed using the whole dataset(dDCE 30min ) and a 5-minute subset of the T1 maps(dDCE 5min ). To test the dDCE models for shortening the LGE wait time, LGE dDCE images were synthesized using the dDCE 5min maps and compared to the clinical LGE images. Remote and MI dDCE parameters on dDCE 30min and dDCE 5min maps were compared to test the model's ability to extract physiological features. Results: dDCE 30min and dDCE 5min map showed a good visuospatial difference between remote and MI(Fig. 1A) and no quantitative difference (Fig.1B). v e and PS showed a significant elevation in MI than in remote (61.12±13.65% vs 13.43±5.00%, P =0.018; 44.62±21.40mL/g/min vs 0.42±0.55mL/g/min, P =0.018, respectively). v p and F p were significantly decreased in MI than in remote (4.17±2.06% vs 10.85±3.77%, P =0.02; 1.11±0.32mL/g/min vs 1.51±0.42mL/g/min, P =0.04, respectively). Representative LGE and LGE dDCE images showed high agreement in the presence of MI (Fig. 2A). Bland-Altman analysis showed good agreement between LGE and LGE dDCE images for the measurement of infarct area (bias, -1.74 ± 6.60 %, Fig. 2B) and transmuraltiy (bias, 1.86 ± 2.73 %, Fig. 2C). The simple liner regression showed strong correlations between LGE and LGE dDCE images for the infarct area (R 2 , 0.95; slope, 0.93, P <0.01; Fig. 2D) and transmurality (R 2 , 0.97; slope, 0.93, P <0.01; Fig. 2E). ROC analysis showed that the AUC was 0.97 (95% CI: 0.94 to 1.00) (Fig. 2F). Increased lesion-blood pool contrast by 10 folds on dDCE images improved subendocardial MI detection (Fig.3). Conclusions: The developed dDCE model provides comparable viability assessment ability to the standard LGE images without the prolonged wait time and reflects MI pathophysiological changes. It shows the potential for a rapid and quantitative myocardial viability imaging protocol using cardiac magnetic resonance.

Global, segmental, and layer-specific two-dimensional speckle tracking echocardiography immediately after acute myocardial infarction as a predictive tool to assess myocardial viability and scar size.

The identification of myocardial scar is key in clinical decision-making after acute myocardial infarction (AMI). However, the gold standard that is cardiac magnetic resonance imaging (CMR) encounters limitations in terms of availability. Two-dimensional speckle tracking echocardiography (2D-STE) may be an accessible alternative in detecting scar and assessing scar transmurality. We aim to evaluate the predictive value of 2D-STE, encompassing measures of global, segmental and layer-specific strain, with respect to myocardial viability and scar size at 6 months follow-up. In 43 patients admitted for primary AMI, we conducted a comparative analysis of strain parameters (including global longitudinal strain (GLS), segmental longitudinal strain (SLS), layer-specific GLS and SLS and the transmural strain gradient from endocardium to epicardium) in relation to conventional echocardiographic parameters at baseline in predicting for scar size and the transmurality index, as measured by CMR, 6 months post enrollment. We demonstrate a moderate correlation between both GLS and conventional echocardiographic parameters, and scar size as well as transmurality index. Wall motion score index exhibited superior predictive performance over GLS and left ventricular ejection fraction in anticipating scar formation. At a cut-off of -13.3% for any scar and -11.5% for transmural scar, SLS can predict scar formation. Layer-specific strain did not provide added predictive value. SLS, but not layer-specific strain, during admission after AMI is an easy and accessible quantitative tool for predicting scar formation and transmurality extent at 6 months follow-up. GLS correlates well with scar size, suggesting its potential utility as a predictive tool.

Magnetic Resonance Myocardial Imaging in Patients With Implantable Cardiac Devices: Challenges, Techniques, and Clinical Applications.

Cardiovascular magnetic resonance imaging (MRI) in patients with cardiac implants, such as pacemakers and defibrillators, has gained importance in recent years with the development of modern cardiac implantable electronic devices. The increasing clinical need to perform MRI examinations in patients with cardiac implants has driven the development of new advanced MRI sequences to mitigate image artifacts associated with cardiac implants. More specifically, advances in imaging techniques, such as wideband late gadolinium enhancement imaging, wideband T1 mapping, and wideband perfusion, have been designed to improve image quality and examinations in patients with cardiac implants, enabling a comprehensive and more reliable diagnosis, which was previously unattainable in these patients. This review article explores recent developments and applications of wideband techniques in the field of cardiovascular MRI, offering insights into their transformative potential. Clinical applications of wideband cardiovascular MRI are highlighted, particularly in assessing myocardial viability, guiding ventricular tachycardia ablation, and characterizing myocardial tissue.

Lesion Characterization by 99mTc-MIBI Myocardial Perfusion Imaging (MPI) & 18F-FDG Cardiac PET Following Myocardial Infarction Before Revascularization & Outcome Prediction: Initial Experience in Bangladesh

99mTc-MIBI SPECT myocardial perfusion imaging (MPI) and 18F-FDG cardiac positron emission tomography (Cardiac PET) can assess the extent and severity of myocardial perfusion and metabolic defect following myocardial infarction (MI) and also able to predict the outcome before revascularization in known coronary artery disease patients. About 135 cases of known coronary artery disease patients were enrolled here for combined nuclear imaging tests, rest only ECG gated MPI and FDG cardiac PET to assess myocardial perfusion and viability status following MI prior to revascularization. In this study we want to figure out the utility of this combined protocol for myocardial lesion characterization and its role for clinical decision-making in-patient selection prior to revascularization and treatment planning. We are also intended to share the initial outcome in available follow up cases. J Inv Clin Cardiol 2023; 5(2): 45-52

Cardiac Repair after Myocardial Infarction is Controlled by a Complement C5a Receptor 1-Driven Signaling Cascade.

Cardiac repair following myocardial infarction is important in regenerating functionally viable myocardium to prevent cardiac death. Previous studies have linked C5aR1 to cardiac regeneration and inflammation. However, C5a receptor-driven responses during the late phases, up to 4 weeks of the infarction insult - a time window that specifically reflects the outcome of the repair process - and the underlying mechanisms are poorly defined. Here, we show that C5ar1, but not C5ar2, deficiency attenuates infarct size following coronary artery ligation-induced myocardial infarction (MI). C5ar1 deficiency limited the deposition of collagen and mitigated cell death in infarcted areas leading to overall improved cardiac function four weeks after MI. While infiltration of neutrophils was reduced in both C5ar1-/- and C5ar2-/- infarcted myocardium 24 h after MI, influx of monocytes after 1 week of MI was reduced only upon C5ar1 deficiency. Subsequent analysis revealed reduced accumulation of myofibroblast, elevated expression of transforming growth factor-beta1 (Tgf-β1) and vascular endothelial growth factor-A (Vegf-A) in C5ar1-/- infarcted hearts. In vitro, exogenous TGF-β1 triggered conversion of fibroblasts into myofibroblasts, which expressed Vegf-A mRNA - an effect that was enhanced upon C5ar1 deficiency. Incubation of C5ar1+/+ or C5ar1-/- endothelial cells (ECs) with supernatants from C5ar1+/+ or C5ar1-/- myofibroblasts respectively, mimicking the in vivo microenvironment in our model, led to significant increase in matrigel tube formation in C5ar1-/- ECs. This was consistent with enhanced neoangiogenesis in C5ar1-/- infarcted hearts. Collectively, our study demonstrates that inhibition of C5aR1 has the potential to improve cardiac function after myocardial infarction.

Non-invasive imaging to guide percutaneous coronary revascularization in chronic total occlusion: a systematic review and meta-analysis

Abstract Background and aims Whether recanalization of coronary chronic total occlusions (CTO) leads to improved patient outcomes is uncertain. We set out to investigate the use of noninvasive imaging modalities to guide patient selection for percutaneous recanalization of coronary chronic total occlusions (CTO-PCI) and its association with outcomes. Methods Systematic review and meta-analysis of studies involving patients undergoing CTO-PCI to detail use of preprocedural non-invasive imaging, change in clinical endpoints and the occurrence of clinical events in these patient cohorts. PubMed and Embase, the Cochrane Database of Systematic Reviews, the PROSPERO database and the Clinical Trials Registry were searched for relevant randomized and observational studies up to May 2023. This study is registered with PROSPERO. The study primary endpoint was a composite of all-cause death and nonfatal myocardial infarction (MI), with a secondary composite endpoint of cardiovascular death, nonfatal MI and target vessel revascularization (TVR). Additional endpoints were individual components of the composite endpoints along with changes in angina burden, LV ejection fraction, ischemic burden, and infarct extent after PCI. Results Of 1264 publications retrieved, 31 studies (26 observational and 5 randomized) were finally included for a total of 7260 patients. Guidance to CTO-PCI varied greatly among included studies, with only a minority implementing routine preprocedural inducible ischemia and myocardial viability assessment. At a median of 3.1 years (range 1-5 years), the primary endpoint occurred at a rate of 3.1 events per 100 patient-years (95%CI: 2.4-3.7). When non-invasive imaging was used to guide CTO-PCI, patients with myocardial ischemia and/or viability, a reduced risk for the primary endpoint was observed (OR 0.3 95%CI 0.2-0.5) compared to CTO-PCI without evidence of myocardial ischemia and/or viability. CTO-PCI was associated with improvements in SAQ summary score, LVEF, reduction of ischemic burden, improvement in myocardial perfusion (all P-values < 0.01), with no change in the burden of myocardial scarring. At meta-regression analysis, a greater improvement in LVEF was observed in studies enrolling patients with lower average baseline LVEF (≤ 45%) (R2 = 63%, p < 0.0001). Conclusions CTO-PCI led to a significant improvement in symptom status (reduction of chest pain) and LV ejection fraction. CTO-PCI guided by the presence of ischemia and/or viability was associated with improved patient outcomes compared with CTO-PCI in the absence of ischemia and/viability, or in patients where non-invasive imaging testing was not performed. Future randomized clinical trials testing whether ischemia and viability-guided CTO-PCI improves clinical outcomes are lacking and warranted.PRISMA Flow diagramGraphical abstract

Perfusion metabolism mismatch predicts short-term complications in Takotsubo syndrome

Abstract Background Takotsubo syndrome (TTS) is a transient cardiac condition triggered by sudden emotional or physical stress characterized by LV dysfunction in the absence of obstructive epicardial coronary artery disease. 123I-BMIPP, an iodinated fatty acid analogue, can identify impaired myocardial metabolic activity. With the use of dual SPECT protocol, reduced uptake of 123I-BMIPP compared to perfusion which is called perfusion-metabolic mismatch is observed in apical regions in TTS. The mismatch may indicate jeopardized but viable myocardium, reflecting transient ischemic damage or metabolically stunned myocardium. However, the association between the perfusion metabolism mismatch in TTS and its complications remains underexplored. Purpose Our study aimed to analyze the degree of perfusion metabolism mismatch at the acute phase in TTS and investigate its association with short-term complications. Methods This retrospective study conducted between 2012 and 2024 at a single center included 82 patients diagnosed with TTS. Patients underwent dual SPECT imaging using 99mTc or 201 Tl and 123I-BMIPP within two weeks of admission. We applied quantitative analysis using QGS/QPS software from Cedars-Sinai. Total perfusion deficit ("TPD") was calculated based on sex-matched normal limits providing the extent of perfusion abnormality. Meanwhile, perfusion-metabolism mismatch scores ("worsen") were determined by comparing the total BMIPP counts to the total counts of perfusion. We then assessed the correlation of these imaging findings with biomarkers, regional wall motion abnormalities, and the occurrence of short-term complications. Short-term complications included heart failure, left ventricular outflow (LVOT) obstruction, mitral regurgitation, cardiac arrhythmia, cardiogenic shock, left ventricle (LV) rupture, and cardiac death during the hospitalization period. Results All study patients exhibited wall motion abnormalities seen in apical segments. The count of myocardial segments with regional wall motion abnormality was correlated with both TPD (r=0.34, p=0.002) and perfusion metabolic mismatch score (r=0.40, p<0.001). TPD had a moderate correlation coefficient with max CK-MB (r=0.44, p<0.001) and troponin T (r=0.40, p<0.001) levels. However, perfusion metabolic mismatch did not display correlations with max CK-MB (r=0.05, p=0.65), and Troponin T (r=0.12, p=0.28) levels. Among 82 patients, 37 patients experienced any short-term complications. Importantly, patients with short-term complications had elevated perfusion mismatch scores compared to those without short-term complications (14.0 [6.0-22.5] vs. 5.0 [3.0-10.0], p<0.001). However, no significant difference was observed in TPD between the two groups (9.0 [4.5-20.0] vs. 7.0 [3.0-12.0], p=0.130). Conclusions Our research highlights a significant association between perfusion-metabolism mismatch and an increased risk for short-term complications in patients with Takotsubo syndrome.

Effect of primary pci in asymptomatic stemi patients presenting 12 to 48 hours of symptom onset, on myocardial viability assessed by spect tc 99m sestamibi scan epitome99

Abstract Background Guidelines on revascularization of asymptomatic stable STEMI patients presenting 12-48 hours of symptom onset are limited. We utilized TC-99mSestaMIBI scan to study the impact of primary PCI on myocardial viability by deriving myocardial salvage index (MSI) from area at risk (AAR), prior to revascularization and final infarct size (FIS) at follow up, in asymptomatic stable STEMI patients presenting between 12-48 hours of symptom onset to PCI. Purpose Evidence contributing lack of symptoms to a non-viable myocardium is lacking and it would be unethical to randomize patients with myocardial infarction (< 48 hours old) to a control arm or a non-intervention arm without evaluating the possibility of salvageable myocardium. Our study aims to inculcate evidence based management of late presenting stable asymptomatic STEMI patients. Methods We enrolled 141 patients presenting with STEMI (12-48 hours), from January 2021 to December 2023, who then underwent TC-99mSestaMIBI scan, followed by revascularization of IRA with 138 patients completing the designed study with follow-up scan at 3 months. Subjects were subcategorised into cohort A(12-24 hrs.), B(25-36 hrs.), and C(37-48 hrs.) according to the duration of symptom onset. Results A substantial MSI of > 0.50 was achieved by 36 %, 8% and 5 % of patients from cohort A, cohort B, and cohort C respectively. Although the AAR was comparable throughout cohorts, on post HOC analysis a statistically significant reduction in the final infarct size was seen among patients in cohort A vs C [Q = 4.72 (p = .00309)], while a reduction of FIS in cohort B and cohort C were obvious but statistically insignificant. Myocardial salvage index was smaller in late presenters, with no statistically significant difference among cohort B & cohort C [Q = 0.96 (p = .77697)]. Delaying the timing of Primary PCI from symptom onset was associated with larger AAR (R= - 0.01) & FIS (R= 0.35) although with a lower correlation coefficient. While evaluating MSI against timing of Primary PCI, a moderately negative (R= - 0.41) relation exists, indicating a linear correlation to reduced myocardial salvage Index with delay in the timing of primary PCI to symptom onset. Conclusion Asymptomatic stable STEMI patients presenting 12-24 hours of symptom onset to PCI, benefited from primary PCI with lesser final infarct size and larger MSI. Despite a comparable AAR across cohorts, MSI fell sharply among patients undergoing primary PCI 24-48 hours of symptom onset with a larger final infarct size, warranting viability guided revascularization. Although primary PCI improved final LVEF and MSI in patients with ischemic heart failure, parameter gain alone was insufficient in endeavoring a positive clinical impact.

The effect of Trimetazidine on the left ventricular global longitudinal strain assessed by cardiac magnetic resonance in stable angina patients with previous myocardial infarction and left ventricular

Abstract Introduction Trimetazidine (TMZ) is an anti-ischemic metabolic agent that is indicated in adults as add-on therapy for the symptomatic treatment of patients with stable angina pectoris (SA). Global left ventricular (LV) systolic function is an important predictor of outcomes in patients after myocardial infarction (MI). Cardiac magnetic resonance (CMR) imaging has now evolved into a major tool for the evaluation of patients with LV dysfunction, providing precise measurements of ejection fraction (EF) and viability assessment but also now allowing assessment of global longitudinal strain (GLS) from standard cine CMR images. We hypothesized that the use of TMZ 80 mg as an anti-ischemic agent in patients with SA, history of MI, reduced EF and in the presence of viable myocardium may produce an early modification of GLS. Methods TRIM-AZ - was a non-interventional, prospective Azerbaijan study to analyze the capacity of short-term therapy with TMZ 80 mg on LV GLS evaluated by CMR in patients with previous MI. Patients with a confirmed diagnosis of heart failure (HF) with impaired LV systolic function and SA in the presence of viable myocardium were included. The treatment of all patients was optimized according to the latest ESC guidelines before entry in the study. Patients were randomized into two groups, one received TMZ 80 mg on top of guidelines directed medical therapies, and the other was the control group. A CMR as well as a transthoracic echography were performed for all patients at the inclusion visit and 8 weeks later. Results 52 patients were included in the study, 30 patients in the TMZ group and 22 in the control group,. At baseline, the mean age was 62±7 years , 63% were smokers, 60% hypertensive, 60% diabetics, 48% had a family history of MI, 12% had typical symptoms of SA while 88% had atypical form (e.g. like shortness of breath). All patients received baseline therapy with ARNI/ACE-i, SGLT2 inhibitors, beta-blockers, MRA, ASA, and statin. 8 weeks after the initiation of TMZ, there were no significant changes in LVEF assessed both by Echo and CMR (29,8%±3,2% vs 30,1%±3,5% by echo in TMZ group; 31,3%±2,7% vs 31,6%±2,7% by echo in the control group; 25,9%±3,1% vs 26,9±4,1% by CMR in TMZ group; 26,9%±2,1% vs 30,1%±2,3% by CMR in the control group), however GLS was significantly improved in TMZ group (-9,9%±1,1% to -12,7%±1,2%, p=0,00), but not in control group (-9,3%±1,3% vs -10,3%±1,4% p=0,3). No adverse event related to TMZ use was reported during the study. Conclusion These findings suggest that the use of trimetazidine in patients with stable angina , previous MI and heart failure in the presence of viable myocardium could improve the left ventricular global longitudinal strain assessed by CMR.

Mechanisms leading to peri-procedural myocardial infarction in patients with focal versus diffuse coronary artery disease

Abstract Background PMI are characterized by an elevation in cardiac biomarkers, such as troponin, following PCI. Adherence to the 4th UDMIof PMI necessitates not only elevated cardiac biomarkers but also the presence of ECG changes, new loss of viable myocardium, or angiographic findings indicative of a procedural complication. Understanding the mechanisms underlying PMI and their associated factors is of paramount clinical significance. Our goal was to investigate the specific pathways contributing to the occurrence of PMI in stable patients undergoing PCI. Methods This prospective study was performed at 23 sites and enrolled patients with at least one epicardial lesion with an FFR≤0.80 planned to be treated by PCI. Each patient underwent a standardized physiological protocol, including manual FFR pullbacks with PPG calculation for the characterization of CAD patterns. The median PPG value (0.62) was used to divide patients into predominantly focal or diffuse disease. Troponin levels were measured after PCI, and patients exhibiting an elevation exceeding 5 times the upper limit of normal (ULN) were subject to evaluation by an independent clinical events committee. In addition, patients with large troponin elevation (>70 times above the ULN) were adjudicated as PMI as a standalone criterion. The primary objective was to investigate the mechanism leading to PMI in patients with focal versus diffuse CAD. Results Overall, 855 patients were included in this analysis, with 34.5% (295 patients) exhibiting a troponin elevation exceeding 5 times the ULN. Among these cases, 66 (7.7%) were adjudicated as PMI. The prevalence of secondary criteria for PMI was as follows: ECG changes at 7.6% (5/66), new loss of viable myocardium at 0%, side branch occlusion at 18.2% (12/66), and large troponin elevation at 84.8% (56/66). Diffuse disease (PPG < 0.62) was significantly associated with PMI (OR 1.71, 95% CI 1.03 to 2.88, p-value = 0.038). In the overall population, the occurrence of ECG changes after PCI was 0.7% in focal disease compared to 0.8% in diffuse disease (p-value=1.0). Side branch occlusion after PCI was observed in 0.7% in focal disease vs. 2.5% in diffuse disease (p-value=0.04), and large troponin elevation occurred in 4.8% in focal disease vs. 8.5% in diffuse disease (p-value=0.03). Additionally, PPG was significantly associated with the incidence of side branch occlusion (OR 1.71, 95% CI 1.03 to 2.88, p-value=0.038) and large troponin elevation after PCI (OR 1.83, 95% CI 1.06 to 3.22, p-value=0.038). Conclusion The presence of diffuse atherosclerosis, as defined by PPG, was linked to an increased risk of PMI. The mechanisms leading to PMI differed between patients with focal and diffuse disease. Patients with diffuse disease demonstrated a higher incidence of branch occlusion and large troponin elevation following PCI compared to those with focal CAD. Targeting patients with high PPG may improve outcomes after PCI.MACE by PPG

Prognostic value of additional midwall late gadolinium enhancement in patients with ischemic cardiomyopathy

Abstract Background Although several studies have reported the additional presence of midwall late gadolinium enhancement (LGE) using cardiac magnetic resonance (CMR) in patients with ischemic cardiomyopathy (ICM), its prognostic value is not well established. Purpose To assess the prognostic value of the additional presence of midwall-LGE in a large cohort of patients with ICM and reduced left ventricular ejection fraction (LVEF). Methods Between 2008 and 2022, all consecutive patients referred for myocardial viability assessment using CMR with an history of ICM (≥70% stenosis in ≥1 epicardial coronary vessel on angiography and/or history of myocardial infarction and/or coronary revascularization) and LVEF <50% were included. Midwall-LGE was defined by non-ischemic LGE corresponding to non-specific myocardial fibrosis. All patients with a history of acute myocarditis and/or sub-epicardial LGE were excluded. The primary outcome was all-cause death. Nested Cox proportional hazard models were used to assess the prognostic value of additional midwall-LGE including its location (lateral and/or septal and other location) and extent (1 or ≥2 segments), above the presence of ischemic-LGE and traditional prognostic factors. The incremental prognostic value of midwall-LGE extent and location was assessed by the C-statistic increment, the continuous net reclassification improvement (NRI), the integrative discrimination index (IDI) and the global Chi-2. Results Among the 6,082 included patients (65±12 years, 73% males), 702 (11.5%) had an additional midwall-LGE. During a median follow-up of 9 (IQR, 7-12) years, 652 (11%) patients died. The presence of midwall-LGE alone was strongly associated with the risk of death compared to patients without midwall-LGE (p<0.001, Figure 1A). Among these patients with midwall-LGE (N=702), survival curves showed an increased risk for midwall-LGE in lateral and/or septal location (p<0.001), for larger extent (p<0.001) and the presence of ischemic-LGE (p<0.001, Figure 1B). In this population with midwall-LGE (N=702), after adjustment for risk factors and extent of ischemic-LGE, midwall-LGE with septal and/or lateral location (adjusted HR: 2.6; 95%CI: 1.8-3.6) and extent ≥2 segments (adjusted HR: 2.6; 95%CI: 1.8-3.7, both p<0.001) were independently associated with all-cause death. A comprehensive LGE model combining all the characteristics of midwall-LGE showed the best improvement in model discrimination and reclassification above traditional prognosticators (C-statistic improvement: 0.13; NRI=46%; IDI=19%, Chi-2 global=261, all p<0.05; LR-test p<0.001, Figure 2). Conclusion In a large cohort of ICM patients, the presence of an additional non-ischemic midwall-LGE is an independent prognosticator of all-cause death, particularly for larger extent or when present in the septal and/or lateral location.Prognostic value of midwall-LGEIncremental prognostic value

Percutaneous revascularization in late-presenting STEMI with absence of viability: effects on left ventricular remodeling and scar

Abstract Introduction In patients with ST-elevation myocardial infarction (STEMI), percutaneous coronary intervention (PCI) should be conducted within 12 hours of symptom onset. The potential benefits attributable to late reperfusion in STEMI fall under the "open artery hypothesis" where the stunned peri-infarction zone after revascularization would restore blood supply and contractility. Purpose To estimate the differences on the LV ejection fraction (LVEF), indexed LV end-systolic volume (iLVESV) and scar in patients with STEMI without viabilitity randomized to optimal medical therapy (OMT) alone or OMT and a late percutaneous coronary intervention (PCI) performed between 24 hours and 30 days after the event. Methods Patients with non-reperfused STEMI were evaluated from September 2021 to June 2022 at a tertiary cardiology hospital. The patients underwent Cardiac Magnetic Resonance (CMR) to assess myocardial viability and were classified as non-viable if they had only 1 wall segment with less than fifty percent thickness of the affected wall with late gadolinium enhancement. The patients were randomized to PCI or OMT alone. CMR was repeated at 6 months to evaluate LVEF, iLVESV and fibrosis. This summary presents a planned partial analysis of the 6-month results (N=51). Descriptive statistics analysis included central and dispersion estimators, or absolute and relative frequencies. To explore the differences between groups and time, Mann-Whitney and Wilcoxon tests were run, and results were given as point-estimates and confidence intervals at 95% (95% CI). A significance level of 5% was adopted for inferential analysis. Results 51 patients (60±11 years, 71% male) were included in the analysis. Of this total, 24 were randomized to PCI + OMT, and 27 to isolated OMT. The groups showed balanced distribution regarding clinical characteristics and initial CMR parameters (LVEF, iLVESV, and fibrosis). The difference in LVEF at the end of 6 months between the OMT and PCI groups was 2.07%, favoring the OMT group; however, this difference was not significant (p= 0.677, 95% CI: -5 to 10). Between the groups, the difference at the end of 6 months in iLVESV was -6.82 ml/m², also without statistical significance (p= 0.858, 95% CI: -19 to 11). There was a significant reduction in the amount of fibrosis in both PCI group with -14.68g (p= 0.011) and in the OMT group with -12.57g (p= 0.009). Detailed results are presented in Table 1. Conclusion Despite a significant reduction in fibrosis in both groups, there was no superiority observed in late PCI compared to isolated OMT in reducing reverse remodeling and fibrosis in patients with non-viable STEMI when compared to isolated OMT.Remodeling changes.

Impact of CT attenuation correction on viable myocardium detection in combined SPECT and PET/CT: A retrospective cohort study.

The influence of computed tomography attenuation correction (CTAC) on the accuracy of diagnosing viable myocardium using Tc-99m-MIBI dedicated cardiac cadmium-zinc-telluride (CZT) single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) combined with F-18-FDG Positron Emission Tomography/Computed Tomography (PET/CT) metabolic imaging, compared with conventional SPECT MPI, remains to be fully elucidated. To evaluate the impact of CTAC on the accuracy of diagnosing viable myocardium using Tc-99m-MIBI dedicated cardiac CZT SPECT MPI combined with F-18-FDG PET/CT, compared to conventional SPECT MPI. 193 patients underwent CZT SPECT and F-18-FDG PET/CT imaging, while 39 patients underwent conventional SPECT and F-18-FDG PET/CT imaging, with both groups utilizing CT for attenuation correction. The injured myocardium (hibernating and scarring) was quantified using the Q.PET software. After CTAC, both groups showed significant improvements in perfusion of the injured myocardial areas, particularly in the inferior wall (INF). The reduction in perfusion was more notable in the CZT SPECT group than that in the conventional group, particularly in the inferior and lateral walls. Among patients with large cardiac chambers, those undergoing MPI with CZT, with normal weights, or males, hibernating myocardium (HM) and scar post-CTAC reductions were particularly significant in the INF. If HM ≥ 10% is considered an indicator for recommended revascularization, among the 87 patients without prior cardiac bypass, 25 (28.7%) might not require revascularization treatment. Dedicated cardiac CZT SPECT and conventional SPECT MPI combined with F-18-FDG PET/CT significantly influenced the assessment of viable myocardium. The impact of CTAC was more profound in dedicated cardiac CZT SPECT, particularly in the INF region. CTAC significantly enhances the accuracy of viable myocardial assessment and may influence clinical decisions regarding revascularization therapy. Therefore, CTAC should be routinely used in dedicated cardiac CZT SPECT MPI combined with F-18-FDG PET/CT for myocardial viability diagnosis.

A refined TTC assay precisely detects cardiac injury and cellular viability in the infarcted mouse heart

Histological analysis with 2,3,5-triphenyltetrazolium chloride (TTC) staining is the most frequently used tool to detect myocardial ischemia/reperfusion injury. However, its practicality is often challenged by poor image quality in gross histology, leading to an equivocal infarct-boundary delineation and potentially compromised measurement accuracy. Here, we introduce several crucial refinements in staining protocol and sample processing, which enable TTC images to be analyzed with light microscopy. The refined protocol involves a two-step TTC staining process (perfusion and immersion) and subsequent Zamboni fixation to differentiate myocardial viability and necrosis, and use of Coomassie brilliant blue to label area-at-risk. After the duo-staining steps were completed, the heart sample was embedded and sliced transversally by a cryostat into a series of thin sections (50 µm) for microscopic analysis. The refined TTC (redTTC) assay yielded remarkably high-quality images with striking color intensity and sharply defined boundaries, permitting unambiguous and reliable delineation of the infarct and area-at-risk. In the same animals, the redTTC assay showed good agreement with the in-vivo gold standard measurements (LGE and MEMRI). Meanwhile, redTTC imaging allows tracking of viable cardiomyocytes at cellular resolution, and with this enhanced capability, we convincingly demonstrated the pro-survival action of stem cells based-therapy. Therefore, the redTTC assay represents a significant technical advance that permits precise detection of the true extent of cardiac injury and cardiomyocyte viability. This approach is cost-effective and may be adapted for use in diverse applications, making it highly appealing to many laboratories performing ischemia/reperfusion injury experiments.

Feasibility of shortening scan duration of 18F-FDG myocardial metabolism imaging using a total-body PET/CT scanner

PurposeTo evaluate 18F-FDG myocardial metabolism imaging (MMI) using a total-body PET/CT scanner and explore the feasible scan duration to guide the clinical practice.MethodsA retrospective analysis was conducted on 41 patients who underwent myocardial perfusion-metabolism imaging to assess myocardial viability. The patients underwent 18F-FDG MMI with a total-body PET/CT scanner using a list-mode for 600 s. PET data were trimmed and reconstructed to simulate images of 600-s, 300-s, 120-s, 60-s, and 30-s acquisition time (G600-G30). Images among different groups were subjectively evaluated using a 5-point Likert scale. Semi-quantitative evaluation was performed using standardized uptake value (SUV), myocardial to background activity ratio (M/B), signal to noise ratio (SNR), contrast to noise ratio (CNR), contrast ratio (CR), and coefficient of variation (CV). Myocardial viability analysis included indexes of Mismatch and Scar. G600 served as the reference.ResultsSubjective visual evaluation indicated a decline in the scores of image quality with shortening scan duration. All the G600, G300, and G120 images were clinically acceptable (score ≥ 3), and their image quality scores were 4.9 ± 0.3, 4.8 ± 0.4, and 4.5 ± 0.8, respectively (P > 0.05). Moreover, as the scan duration reduced, the semi-quantitative parameters M/B, SNR, CNR, and CR decreased, while SUV and CV increased, and significant difference was observed in G300-G30 groups when comparing to G600 group (P < 0.05). For myocardial viability analysis of left ventricular and coronary segments, the Mismatch and Scar values of G300-G30 groups were almost identical to G600 group (ICC: 0.968-1.0, P < 0.001).ConclusionSufficient image quality for clinical diagnosis could be achieved at G120 for MMI using a total-body PET/CT scanner, while the image quality of G30 was acceptable for myocardial viability analysis.

A Feasibility Study of [18F]F-AraG Positron Emission Tomography (PET) for Cardiac Imaging-Myocardial Viability in Ischemia-Reperfusion Injury Model.

Myocardial infarction (MI) with subsequent inflammation is one of the most common heart conditions leading to progressive tissue damage. A reliable imaging marker to assess tissue viability after MI would help determine the risks and benefits of any intervention. In this study, we investigate whether a new mitochondria-targeted imaging agent, 18F-labeled 2'-deoxy-2'-18F-fluoro-9-β-d-arabinofuranosylguanine ([18F]F-AraG), a positron emission tomography (PET) agent developed for imaging activated T cells, is suitable for cardiac imaging and to test the myocardial viability after MI. To test whether the myocardial [18F]-F-AraG signal is coming from cardiomyocytes or immune infiltrates, we compared cardiac signal in wild-type (WT) mice with that of T cell deficient Rag1 knockout (Rag1 KO) mice. We assessed the effect of dietary nucleotides on myocardial [18F]F-AraG uptake in normal heart by comparing [18F]F-AraG signals between mice fed with purified diet and those fed with purified diet supplemented with nucleotides. The myocardial viability was investigated in rodent model by imaging rat with [18F]F-AraG and 2-deoxy-2[18F]fluoro-D-glucose ([18F]FDG) before and after MI. All PET signals were quantified in terms of the percent injected dose per cc (%ID/cc). We also explored [18F]FDG signal variability and potential T cell infiltration into fibrotic area in the affected myocardium with H&E analysis. The difference in %ID/cc for Rag1 KO and WT mice was not significant (p = ns) indicating that the [18F]F-AraG signal in the myocardium was primarily coming from cardiomyocytes. No difference in myocardial uptake was observed between [18F]F-AraG signals in mice fed with purified diet and with purified diet supplemented with nucleotides (p = ns). The [18F]FDG signals showed wider variability at different time points. Noticeable [18F]F-AraG signals were observed in the affected MI regions. There were T cells in the fibrotic area in the H&E analysis, but they did not constitute the predominant infiltrates. Our preliminary preclinical data show that [18F]F-AraG accumulates in cardiomyocytes indicating that it may be suitable for cardiac imaging and to evaluate the myocardial viability after MI.

Secondary mitral regurgitation surgical management: a narrative review.

The most common valvular heart disease in the US is moderate to severe mitral regurgitation (MR). Function MR or secondary MR comprises many of these cases. Moderate and severe secondary MR are independently associated with increased all-cause mortality and rehospitalization for heart failure. Both ischemic and nonischemic cardiomyopathy can cause secondary MR via similar pathophysiology that leads to inadequate valve leaflets coaptation. The management of secondary MR is complex. The optimal treatment strategy for secondary MR remains controversial, reflected in the vast array of treatment options and the complexity of therapeutic decision-making. Several surgical mitral valve repair techniques have been described in the literature. Many of these aims to facilitate adequate valve leaflet coaptation. In this review, the pathophysiology of MR is described with a focus on evaluating and managing secondary MR. A literature review was performed using PubMed and Google Scholar. Clinical trials, meta-analyses, randomized controlled trials, reviews, and systematic reviews were considered from January 1, 1995 through December 31, 2022. Articles published in languages other than English with limited text availability were excluded. Optimal therapeutic approach in severe secondary MR is complex and several patient factor should be considered. We provide a framework for the surgical management of secondary MR based on echocardiographic parameters, the presence of ischemia, and myocardial viability. Further study is needed to guide the selection of patients most likely to benefit from mitral valve repair or replacement in the setting of secondary MR.

Cardioprotective Action of the JNK Inhibitor Tryptanthrin Oxime in the Late Period after Myocardial Infarction.

In experiments on Wistar rats, the effect of a new selective JNK inhibitor tryptanthrin oxime (TR-Ox) on parameters of systemic hemodynamics, cardiohemodynamics, and post-infarction fibrosis was studied 4 months after acute myocardial ischemia (1 h) followed by reperfusion. TR-Ox was administered intraperitoneally at a dose of 12 mg/kg 20 min before reperfusion, and then once a day for the next 4 days. Administration of TR-Ox to animals in the acute phase of myocardial infarction contributed to more complete preservation of myocardial viability in the delayed period: a relative increase of muscle elements proportion in the scar, a decrease in the formation of connective tissue areas with complete and >50% replacement of the myocardium, and deceleration of fibrotic scarring in myocardium areas distant from the focus of injury, resulting in improved systolic and diastolic myocardial function. Four months after myocardial infarction, significant improvement in systemic hemodynamics and cardiohemodynamics parameters was observed in the group treated with TR-Ox: stroke volume, cardiac output, left ventricular systolic pressure, maximum rates of left ventricle pressure rise and fall significantly increased and the left ventricle end-diastolic pressure decreased in comparison with the corresponding parameters in the control group.

A Methodology to Measure Glucose Metabolism by Quantitative Analysis of PET Images.

Positron emission tomography (PET) with F-18 fluorodeoxyglucose (FDG) tracer is the standard clinical technique to measure myocardial and vessel metabolism and viability and to investigate the metabolic syndrome associated with cardiovascular diseases. The quantitative analysis of PET images allows one to study the cardiovascular physiological processes, by extracting quantitative parameters from the analysis of the tracer kinetic. Here, we propose a new methodology to quantify and evaluate the evolution of glucose metabolism inside the myocardium and the large vascular structures over time. We merge and analyze PET and CT cardiac images, extracting different volumes of interest (VOI) and performing quantitative measurements. To validate it, we apply the methodology to merge images of the aorta vessel for patients affected by metabolic syndrome. The application of the proposed approach to the use case reveals a correlation between administered drugs and metabolic syndrome, measuring the glucose metabolic rate (MRGlu) in both the myocardium and aorta. The proposed methodology can be used to evaluate some cardiovascular risk indexes of diabetic patients, too. The proposed methodology can also be deployed to analyze other application domains.